The clinical pharmacology of bleomycin administered by continuous intravenous infusion over a 4 to 5 day period was examined in nine patients. Patients receiving 30 units per day attained an average steady state plasma level of 145.8 (f 43.l)ng/ml bleomycin. Elimination of bleomycin was initially described by first order rate kinetics (tY2 = 1.32 f 0.39 hour). However, at times greater than 12 hours following termination of infusion, a second elimination phase was observed ( t E = 8.9 f 2.7 hour). There was also a high correlation between renal bleomycin clearance and creatinine clearance. The importance of renal clearance was indicated in a patient with renal impairment. This patient attained a steady state bleomycin concentration of 1046 ng/ml and exhibited a terminal elimination half-life of 33 hours. Overall plasma clearance of bleomycin (Qp) was generally greater than renal clearance, indicating that a nonrenal clearance mechanism was also important in bleomycin elimination. This nonrenal mechanism became especially apparent during renal failure.
Cancer 40:2772-2778, 1977.
LEOMYCIN IS COMPOSED OF A GROUP OF B glycopeptide antibiotics produced by Streptomyces verticillus. l0 Blenoxane, the bleomycin sulfate used clinically, is a copper-free mixture of several bleomycin species. At least 65% of the mixture is composed of bleomycin A group and the remaining 35% accounted for by the B group. Bleomycin A, and B, are 55-70% and 25-32% of the total weight, respectively.' Clinically, bleomycin has been used as a single agent, or in combination with other antineoplastic agents, against a variety of neoplasms, particularly squamous cell carcinoma, lymphoma and testicular carcinoma.'
The clinical toxicology of bleomycin appears to be primarily associated with cutaneous toxicity, pyrexia, and pulmonary toxicity. A 47% incidence of cutaneous disorders, including alo-